The problem of resistance to a large variety of anti-infective agents by bacterial and fungal pathogens indicates warning sign to infection combating strategies. The defiant nature of these pathogens were mostly associated with the higher extrusion rate of anti-infective agents by transmembrane efflux pumps like NorA (Staphylococcus aureus) to quinolone class of antibacterials like norfloxacin and ciprofloxacin, 1258c (Mycobacterium tuberculosis) to rifampicin, Mde A (S. aureus Mupr-1) to mupirocin, Tet K (S. aureus SA-K2192) to tetracyclin, and Msr A (S. aureus SA-K2191) efflux pump to erythromycin. Therefore, use of suitable efflux pump inhibitor in combination with resistance-susceptible antibacterials in resistant pathogens would re-establish their sensitivity to the same. Large number of synthetic (acrylic acid amides, boronate species and 2-phenyl quinolones) and natural products (piperine and capsaicin) are known to have bacterial efflux pump inhibition properties. Furthermore, these compounds are reported to potentiate the bioefficacy of known drugs by reducing multi-drug resistance via their ability to inhibit efflux pumps (WO 2009/110002 A1, Fontaine, F. et al, J. Med. Chem. 2014, 57, 2536; Sabatini, S. et. al., J. Med. Chem. 2013, 56, 4975; Mirza, Z. M. et. al. J. Med. Microbiol. 2010, 60, 1472; Kalia, N. P. et al., J. Antimicrob. Chemother. 2012, 67, 2401).
Rotenoids are naturally occurring substances containing a cis-fused tetrahydrochromeno[3,4-b]chromene nucleus. Rotenoids are related to the isoflavones. Boeravinone B (6,9,11-trihydroxy-10-methyl[1]benzopyrano[3,4-b][1]benzopyran-12(6H)-one) is a rotenoid class of compound isolated from traditional Indian medicinal plant Boerhavia diffusa Linn (Punernava). In Ayurveda, Boerhavia diffusa is reported to posseess wide variety of medicinal properties including its anti-aging effects. Beside this, the root extract of the Boerhavia diffusa posses antioxidant, hepatoprotective (Olaleye M. T. et al, Food Chem. Tox. 2010, 48, 2200-2205, Prathapan A. et al., J. Food Biochem. 2011, 35, 1548-1554) and cardioprotective properties (Vineetha V. P et al., Cardiovas. Tox. 2013, 13, 123-137; Prathapan A. et al., Br. J. Nutr. 2013, 110, 1201-1210). Compounds isolated from this plant includes alkaloid punernavine which is known to possess various pharmacological activities such as anticancer (Manu K. A et al., Asian Pac. J. Can. Prev. 2009, 10, 1031-1037), antiestrogenic (Sreeja S. et al., J. Ethnopharmacol., 2009, 126, 221-225), immunomodulatory (Manu K. A. et al., Immunopharmacol Immunotoxicol. 2009, 31, 377-387) and antiamoebic activity (Sohni Y. R., et al., J. Ethnopharmacol. 1995, 45, 43-52). Boeravinone A-J are reported to posses anti-inflammatory (WO 2008117230; EP 2139504; IN 2009DN06804; US 20100120902; Bairwa K. et al., J. Nat. Prod., 2013, 76, 1393-1398) and breast cancer resistant protein (BCRP) inhibitory activity (Ahmed-Belkacem A. et al., J. Med. Chem., 2007, 50, 1933-1938). In the present invention, we report the new use of 6,9,11-trihydroxy-10-methyl[1]benzopyrano[3,4-b][1]benzopyran-12(6H)-one for potentiating the bioefficacy of known antimicrobial drugs via inhibition of bacterial efflux pump(s).